Articles: hyperalgesia.
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Comparative Study
Novel Endomorphin Analogs are More Potent and Longer Lasting Analgesics in Neuropathic, Postoperative, Inflammatory, and Visceral Pain Relative to Morphine.
Activation of the mu-opioid receptor provides the gold standard for pain relief, but most opioids used clinically have adverse effects that have contributed to an epidemic of overdose deaths. We recently characterized mu-opioid receptor selective endomorphin (EM) analogs that provide potent antinociception with reduction or absence of a number of side effects of traditionally prescribed opioids including abuse liability, respiratory depression, motor impairment, tolerance, and inflammation. The current study explores the effectiveness of these EM analogs relative to morphine in four major pain models by intrathecal as well as intravenous administration in male Sprague Dawley rats and subcutaneous administration in male CD-1 mice. In the spared nerve injury model of neuropathic pain, mechanical allodynia and mechanical hyperalgesia were assessed with von Frey and Randall-Selitto tests, respectively. In the paw incision model of postoperative pain, von Frey testing was used to assess mechanical allodynia and thermal hyperalgesia was evaluated with Hargreaves testing. In the Complete Freund's Adjuvant model of inflammatory pain, thermal hyperalgesia was assessed using Hargreaves testing. In CD-1 mice, visceral pain was assessed with the acetic acid writhing test. In all cases, EM analogs had equal or greater potency and longer duration of action relative to morphine. The data suggest that EM analogs, particularly analog 4 (ZH853), could provide effective therapy for a diverse spectrum of pain conditions with low risk of adverse side effects compared with currently used opioids such as morphine. ⋯ Novel EM analogs show equal or greater potency and effectiveness relative to morphine in multiple pain models. Together with substantially reduced side effects, including abuse liability, the compounds show promise for addressing the critical need for effective pain relief as well as reducing the opioid overdose epidemic.
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Best Pract Res Clin Anaesthesiol · Dec 2017
ReviewDifferent protocols used today to achieve total opioid-free general anesthesia without locoregional blocks.
With increasing awareness of both short- and long-term problems associated with liberal perioperative opioid administration, the need for routinely and clinically feasible alternatives is greater than ever. Opioid-free anesthesia-previously reserved for bariatric surgery-is receiving increasing attention in mainstream anesthesia. ⋯ For a concrete clinical perspective, we present in depth our opioid-free protocol for bariatric surgery. However, clinicians must be aware of potential problems related to opioid-free anesthesia.
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The Acquisition and Extinction of Fear of Painful Touch: a Novel Tactile Fear Conditioning Paradigm.
Fear of touch, due to allodynia and spontaneous pain, is not well understood. Experimental methods to advance this topic are lacking, and therefore we propose a novel tactile conditioning paradigm. Seventy-six pain-free participants underwent acquisition in a predictable as well as an unpredictable pain context. ⋯ Cue exposure reduced fear of touch, whereas context exposure reduced contextual fear. Thus, painful touch leads to increased fear, as does touch in the same context as unpredictable pain, and extinction protocols can reduce this fear. We conclude that tactile conditioning is valuable for investigating fear of touch and can advance our understanding of chronic pain.
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Best Pract Res Clin Anaesthesiol · Dec 2017
ReviewOpioid-free anesthesia opioid side effects: Tolerance and hyperalgesia.
Opioids are the most potent drugs used to control severe pain. However, neuroadaptation prevents opioids' ability to provide long-term analgesia and produces opposite effects, i.e., enhancement of existent pain and facilitation of chronic pain development. Neuroadaptation to opioids use results in the development of two interrelated phenomena: tolerance and "opioid-induced hyperalgesia" (OIH). ⋯ Conversely, observations of improved patient's recovery after opioid-sparing anesthesia techniques stand as an indirect evidence that perioperative opioid administration deserves caution. To date, perioperative OIH has rarely been objectively assessed by psychophysics tests in patients. A direct relationship between the presence of perioperative OIH and patient outcome is missing and certainly deserves further studies.
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Animal models have previously shown that HIV is associated with hyperalgesia, or heightened sensitivity to painful stimuli. Efforts to determine whether this finding translates to humans are presently lacking. Among persons living with HIV (PLWH), those with detectable viral loads may be at greatest risk for heightened pain sensitivity. It was hypothesized that PLWH with detectable viral loads would be more sensitive to painful stimuli compared with PLWH without detectable viral loads and healthy controls without HIV. ⋯ These preliminary results tentatively suggest that the detectable presence of the virus may sensitize PLWH to painful mechanical and heat stimuli.